Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury

Human umbilical cord mesenchymal stem cells(hUC-MSCs)are a promising candidate for spinal cord injury(SCI)repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources.However,modest clinical efficacy hampered the progression of these cells to clinical translation.This discrepancy may be due to many variables,such as cell source,timing of implantation,route of administration,and relevant efficacious cell dose,which are critical factors that affect the efficacy of treatment of patients with SCI.Previously,we have evaluated the safety and efficacy of 4×10⁶ hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models.To search for a more accurate dose range for clinical translation,we compared the effects of three different doses of hUC-MSCs-low(0.25×10⁶ cells/kg),medium(1×10⁶ cells/kg)and high(4×10⁶ cells/kg)-on subacute SCI repair through an elaborate combination of behavioral analyses,anatomical analyses,magnetic resonance imaging-diffusion tensor imaging(MRI-DTI),biotinylated dextran amine(BDA)tracing,electrophysiology,and quantification of mRNA levels of ion channels and neurotransmitter receptors.Our study demonstrated that the medium dose,but not the low dose,is as efficient as the high dose in producing the desired therapeutic outcomes.Furthermore,partial restoration of theγ-aminobutyric acid type A(GABAA)receptor expression by the effective doses indicates that GABAA receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord.Overall,this study revealed that intrathecal implantation of 1×10⁶ hUC-MSCs/kg is an alternative approach for treating subacute SCI.     

All roads lead to Rome-a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer’s disease

Age-related neurodegenerative disorders such as Alzheimer’s disease(AD)have become a critical public health issue due to the significantly extended human lifespan,leading to considerable economic and social burdens.Traditional therapies for AD such as medicine and surgery remain ineffective,impractical,and expensive.Many studies have shown that a variety of bioactive substances released by physical exercise(called“exerkines”)help to maintain and improve the normal functions of the brain in terms of cognition,emotion,and psychomotor coordination.Increasing evidence suggests that exerkines may exert beneficial effects in AD as well.This review summarizes the neuroprotective effects of exerkines in AD,focusing on the underlying molecular mechanism and the dynamic expression of exerkines after physical exercise.The findings described in this review will help direct research into novel targets for the treatment of AD and develop customized exercise therapy for individuals of different ages,genders,and health conditions.     

Angiotensin-(1–7)reducesα-synuclein aggregation by enhancing autophagic activity in Parkinson's disease

Abnormal accumulation ofα-synuclein contributes to the formation of Lewy bodies in the substantia nigra,which is considered the typical pathological hallmark of Parkinson's disease.Recent research indicates that angiotensin-(1-7)plays a crucial role in several neurodegenerative disorders,including Parkinson's disease,but the underlying mechanisms remain elusive.In this study,we used intraperitoneal administration of rotenone to male Sprague-Dawley rats for 4 weeks to establish a Parkinson's disease model.We investigated whether angiotensin-(1-7)is neuroprotective in this model by continuous administration of angiotensin-(1-7)into the right substantia nigra for 4 weeks.We found that angiotensin-(1-7)infusion relieved characteristic parkinsonian behaviors and reducedα-synuclein aggregation in the substantia nigra.Primary dopaminergic neurons were extracted from newborn Sprague-Dawley rat substantia nigras and treated with rotenone,angiotensin-(1-7),and/or the Mas receptor blocker A-779 for 24 hours.After binding to the Mas receptor,angiotensin-(1-7)attenuated apoptosis andα-synuclein aggregation in rotenone-treated cells.Primary dopaminergic neurons were also treated with angiotensin-(1-7)and/or the autophagy inhibitor 3-methyladenine for 24 hours.Angiotensin-(1-7)increasedα-synuclein removal and increased the autophagy of rotenone-treated cells.We conclude that angiotensin-(1-7)reducesα-synuclein aggregation by alleviating autophagy dysfunction in Parkinson's disease.Therefore,the angiotensin-(1-7)/Mas receptor axis plays an important role in the pathogenesis of Parkinson's disease and angiotensin-(1-7)has potential therapeutic value for Parkinson's disease.All experiments were approved by the Biological Research Ethics Committee of Nanjing First Hospital(approval No.DWSY-2000932)in January 2020.     

AN UNUSUAL BILATERAL VAGAL PARAGANGLIOMAS： ONE CASE STUDY

VAGAL paraganglioma VP)is an uncommonneoplasm originating from neural crest paragan-glion cells located along the vagus nerve,repre-senting less than5%of all paragangliomas of the head andneck.1Despite improvement in microsurgical techniques,management of…     

Analysis of brain-stem auditory evoked potential and visual evoked potential in patients with Parkinson disease

INTRODUCTION The exact cause of Parkinson disease (PD) has not been known yet[1]. The overwhelming progress had been made in the treatment and pathogenesis of PD in recent 30 years, especially 10 years[2]. But it is still no way now to prevent or postpone…     

Evaluation of corticospinal tract injury with three-dimensional diffusion tensor tract in patients with acute cerebral infarction

Three-dimensional diffusion tensor tract (DTT) is the newest imaging to describe the structure of white matter fiber in three-dimensions, it has great significance in dividing the concrete anatomic site of gray and white matter lesions, displaying the correlation with fibrous band and judging clinical prognosis, which is incomparable by other imagings.OBJECTTVE: To observe the conditions of corticospinal tract (CST) in acute cerebral ischemic stroke patients,and analyze the relationship between motor function and the severity of CST injury.DESIGN: A case-control observation.SETTTNG: Department of Medical Imaging, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA.PARTTCTPANTS: Fifteen patients with acute cerebral infarction were selected from Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA from February to December in 2005. They all suffered from acute attack and motor disorder of hemiplegic limbs to different extent, and were conformed by CT or MRI.There were 9 males and 6 females, aging 16-87 years old, the median age was 51.7 years, and all were right handed. Fifteen right-handed normal subjects, who were matched by age and sex with the patients in the cerebral infarction group, were selected from the relatives of patients and physicians of the Imaging Department as the control group. All the subjects were informed and agreed with the study.METHODS: The patients with acute cerebral infarction and subjects in the control group received MR diffusion tensor imaging (DTI) with GE 1.5 T nuclear magnetic resonance system, fiber tracking with the software of dTV- Ⅱ. Fractional anisotropy (FA) maps and three-dimensional tractography of bilateral CST of all patients were created. Displacement, continuity and destroy of fibrous bands were observed. At the same time, muscle strength of ipsilateral hand of patients with cerebral infarction was measured with Brunnstrom standard. The correlation between the severity of CST injury and the muscle strength of ipsilateral hand was analyzed with spearman correlation analysis.MAIN OUTCOME MEASURES: ① FA values in the infarcted sites and those in the contralateral corresponding sites of patients with cerebral infarction; ② CST manifestations in the patients with cerebral infarction and the control group.RESULTS: All the 30 testees were involved in the analysis of results. ① The FA values in infarcted sites of white matter were significantly lower than those in the contralateral ones (t =4.570, P ＜ 0.001 ). ② In the control group, bilateral CST were reconstructed, they originated from precentral gyrus, went downwards to internal capsule, and extended to pontine and medulla oblongata, each fiber had good uniformity in continuous form. In the patients with cerebral infarction, the forms of contralateral CST were consistent with those in the control group with good continuity. Due to the involvement by the infarcted site to different extents, the ipsilateral CST manifested as continuous interruption and loss of uniformity in anatomic structure and form. The CST involvements were divided into three grades: integrated CST for grade I (n =2); integrated CST but compressed or displaced for grade 2 (n =5); interrupted CST for grade 3 (n =8). ③ The severity of CST injury was obviously correlated with the muscle strength of the ipsilateral hand (r=0.888, P＜ 0.05＝.CONCLUSION: ① CST is injured to different extents in patients with acute cerebral infarction, and the severity of injury is associated with muscle strength. It is indicated that it can be used to judge the prognosis of rehabilitative treatment. ②DTT can directly display the status of pyramidal tract more three-dimensionally.     

利多卡因在人工流产中的应用

人工流产作为避孕失败的补救措施，是在孕早期进行的的一种简便有效的手术，不需麻醉，门诊进行，合并症少。但因为术中扩宫及吸宫时受到机械刺激而引起疼痛，部分病人出现人流综合症。针对这种情况，我院选择部分人工流产病人实施官颈旁阻滞麻醉，现总结如下：